Our objective is to develop and exploit the synthetic polyanion, polystryrene sulfonate (PSS), a known anti-tumor agent, as a tool for studying (1) the structure and function of the nucleus and (2) macromolecular interactions during cell growth and differentiation. We will study the cytochemistry and electron microscopy of the male mealy bug cell, in which the five maternal chromosomes appear as diffuse euchromatin and the five paternal chromosomes are heterochromatic and genetically inactive. Having observed enhancement of RNA synthesis and deheterochromatization with PSS, and having characterized the effect in situ of PSS on histone and DNA, we will utilize PSS and actinomycin D to study the nature of histone repression of DNA in situ by light autoradiography, and develop a method for localizing specific genetic activity to specific gene sites. We will utilize organ explants and embryonated eggs to study developmental alteration of heterochromatin with PSS. In isolated calf-thymus nuclei and erythrocytes, having biochemically determined the specificity of the PSS - histone interaction, we will correlate both structural changes and functional changes with the complexing of specific histones and determine the kinds of RNA produced. In zebra fish we will investigate the transcriptional potential during early embryogenesis using PSS Actinomycin D.